Unlike a normal cell of which division and proliferation are well-controlled according to needs of an individual, cancer commonly means diseases that form many abnormal cells through unrestrained division and proliferation due to mutation caused by several carcinogenetic factors and changes in the intercellular environment in genes related to cell growth to invade the surrounding tissue and organs, thereby causing neoplasia and destruction of the normal tissue (Lopez A. D., et al., Lancet, 367:1747-1757, 2006).
Colon cancer, which is one of the carcinomas and includes rectal cancer, colon cancer, and anal cancer, shows high mortality rate in the United States, which is a representative of a developed country (Shike M, et al., Bull World Health Organ, 68: 377-385, 1990; UK Bowel Cancer Incidence Statistics, at info.cancerresearchuk.org/cancerstats/types/bowel/incidence, last visited Apr. 24, 2009.
Symptoms of colon cancer are not specific to only large intestine. Therefore, it may be difficult to assert which symptom is a characteristic symptom indicating colon cancer. However, generally, colon cancer patients have symptoms such as a change in bowel habits, bloody stool or mucous stool (mucous is mixed in stool), thinner stool, weight loss, abdominal discomfort (abdominal pain, abdominal distension), fatigue, loss of appetite, vomiting, nausea, anemia, or the like. Such as all of the cancer, in the case of colon cancer, when it is detected early and appropriately treated, colon cancer may also be completely cured.
However, most colon cancers do not show any symptom during early stage of colon cancer, and in the case in which some symptom appears due to colon cancer, generally, colon cancer has already significantly progressed. The reason is that in the early stage of colon cancer, a size of cancer is small and no symptoms appear, but in the case in which the cancer grows and the size thereof becomes large, the cancer blocks the stool from passing in the large intestine, bleeding occurs in the growing colon cancer, and secretion is secreted from the surface of colon cancer. As a colon cancer screening test currently used, there are a fecal occult blood test, a tumor marker test, a barium enema, a colonoscopy, a computed tomography (CT), an abdomen ultrasonography, a transrectal ultrasonography, and a sigmoidoscopy test, but these tests have several limitations in the early diagnosis. Considering that a survival rate for stage 1 is 90% or more but a survival rate for stage 4 in which the cancer has already spread to distant organs such as the lung, liver, or the like, drops to below 5%, in order to improve the survival rate of colon cancer patients, a method of more accurately and detecting early colon cancer needs to be developed. To this end, a diagnostic system capable of improving accuracy is required, which requires identification of colon cancer-related marker genes. In addition, in the case of colon cancer development, the colon cancer marker may be appropriately used to predict prognosis and determine treatment strategy.
It is known that changes in various genes such as various kinds of oncogenes, tumor suppressor genes, and the like, are involved in the process of the carcinogenesis of colon cancer. Actually, colon cancer is cancer of which genetic changes occurring in the process of carcinogenesis have been well identified. In colon cancer, a change in a single oncogene or tumor suppressor gene may not cause cancer alone. When normal large intestinal epithelium progresses to colon cancer through an adenoma stage, changes in various cancer-related genes need to be accumulated over a long period of time, that is, over several years, which is called multistage changes in genes in the carcinogenesis of colon cancer. Here, the important thing is not a change sequence of genes at each stage but the total sum of changes ultimately accumulated in the genes. Examples of genetic changes involved in the carcinogenesis of colon cancer include K-ras gene mutations, adenomatous polyphosis coili (APC) gene mutations, mutated in colon cancer (MCC) gene mutations, deleted in colon cancer (DCC) gene on chromosome 18, p53 gene mutations on chromosome 17, and deoxyribonucleic acid (DNA) methylation disorder, and the like, and mutations in human Mut S homologue 2 (hMSH2) gene, hMSH1 gene, human post-meiotic segregation 1 (hPMS1) gene, hPMS2 gene are involved therein.
The European Group on Tumor Markers (EGTM) guidelines for clinical use of markers in colon cancer was reported by European researchers in 2003 (Duffy M. J., et al., Eur. J Cancer 39: 718-727, 2003). This guideline individually focuses on carcinoembryonic antigen (CEA), which is a serum marker. In addition to the CEA, carbohydrate antigen 19.9 (CA19.9), CA 242, tissue inhibitor of metalloproteinase type 1 (TIMP-1), Ras, p53, thymidylate synthase (TS), Musashi (MSI), DCC, or the like, have been suggested as the marker, and the evidences have been proven, but cancer-specific characteristics are still not founded therein (Duffy M. J., et al., Eur. J. Cancer 43:1348-1360, 2007).
As described above, since development of the carcinogenesis is complexly related to various genes, expression of these genes, and a mechanism of regulation thereof, researches into a technology of identifying a marker for new diagnosis and treatment of the cancer by comparing expression rates of cancer-related genes using an oligo-chip using a large amount of genes have been recently conducted. Genes of which expression increases or decreases in cancer cells are involved in various processes such as cell division, cell signaling, cytoskeleton, cell movement, cell defense, gene and protein expression, intracellular metabolism in cancer cells, and the like. There are some genes having the same expression changes as that of each patient, but there are many genes having different expression changes according to the patient's tissue. Specificity of each patent may be the most likely reason. Therefore, accurate pathological findings and classification for the tissue of the studied target patient has been required, and detection and identification of new genes has been further required for more accurate diagnosis using genes.